The purpose of this study is to determine whether thymic transplantation can restore immune function in patients with complete DiGeorge syndrome. DiGeorge syndrome in characterized by defects in the heart, parathyroid, and thymus. Complete DiGeorge syndrome are those patients with no proliferative responses (of peripheral blood mononuclear cells) to mitogen stimulation. We have transplanted two patients with complete DiGeorge syndrome. We now have over 3 years of followup on our first patients. The second patient died after the transplant from medical complications related to laryngeal malacia. The immune results of the first patient are in press. T cell function developed in this patient beginning at 7 months after the transplant. This report will focus on data obtained in the past year. The patient's CD3 T cell count increased over the past year to over 500/mm3. More importantly, the patient has normal T cell function as measured by T cell proliferative responses to mitogens, normal responses in mixed lymphocyte reactions, and normal proliferative responses to tetanus after immunization. The patient's serum immunoglobulins have normalized. The patient responds with normal titers to immunization with tetanus and pneumovax. The patient is tolerant of the thymus donor, showing that the donor thymus functioned in the development of T cell function. All of the developing T cells in the patient's periphery have been host in origin. These data plus the thymic transplant biopsy reported earlier, lead us to conclude that the restoration of T cell function in this patient was secondary to thymopoeisis of host T cells in the donor graft. The second patient was quite different. He developed T cells within the first month of transplantation. These were shown to be functional as assessed by proliferative responses to the mitogen PHA. When the patient died from an intraventricular hemorrhage of uncertain etiology, an autopsy was performed. We showed earlier that most of the T cells that proliferated in this patient were donor in origin. Over the past year, we have assessed the condition of the thymic graph using immunohistochemical techniques. We did not find evidence of thymopoeisis. We concluded that immunity was restored in this patient by adoptive transfer of donor thymocytes. In summary there are two mechanisms for immune restoration after thymic transplantation in complete DiGeorge syndrome: host thymopoeisis and adoptive transfer of donor thymocytes. SIGNIFICANCE: The results of thymic transplantation give "proof of principle" that thymopoiesis can occur in transplanted donor thymic epithelium. We are expanding this therapy to patients with partial DiGeorge syndrome and patients with HIV infection. Regarding the latter group of patients, we have just begun a clinical trial of thymic transplantation in HIV infection. The complete DiGeorge patients act as the control for HIV patients.